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25 results on '"Brewer, Matthew G."'

4. Electrical Impedance Spectroscopy Quantifies Skin Barrier Function in Organotypic In Vitro Epidermis Models

Author

van den Brink, Noa J.M., primary, Pardow, Felicitas, additional, Meesters, Luca D., additional, van Vlijmen-Willems, Ivonne, additional, Rodijk-Olthuis, Diana, additional, Niehues, Hanna, additional, Jansen, Patrick A.M., additional, Roelofs, Susan H., additional, Brewer, Matthew G., additional, van den Bogaard, Ellen H., additional, and Smits, Jos P.H., additional

Published
2024
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15. JAK Signaling Is Critically Important in Cytokine-Induced Viral Susceptibility of Keratinocytes.

Author

Arnold, Kimberly A., Peterson, Liam F., Beck, Lisa A., and Brewer, Matthew G.

Subjects
HUMAN herpesvirus 1, VACCINIA, KERATINOCYTES, VIRUS diseases, SKIN diseases
Abstract

Little is known about whether type 1 (IFNγ), 2 (IL-4/IL-13), or 3 (IL-17A/IL-22) cytokines affect the susceptibility of keratinocytes (KC) to viruses. These immune pathways predominate in various skin diseases: lupus, atopic dermatitis (AD), and psoriasis, respectively. Janus kinase inhibitors (JAKi) are approved to treat both AD and psoriasis, and are in clinical development for lupus. We evaluated whether these cytokines alter viral susceptibility of KC and determined if this effect is modulated by treatment with JAKi. Viral susceptibility to vaccinia virus (VV) or herpes simplex virus-1 (HSV-1) ± JAKi was assessed in immortalized and primary human KC pretreated with cytokines. Exposure to type 2 (IL-4 + IL-13) or the type 3 (IL-22) cytokines significantly increased KC viral susceptibility. Specifically, there was a peak increase of 12.2 ± 3.1-fold (IL-4 + IL-13) or 7.7 ± 2.8-fold (IL-22) in VV infection as measured by plaque number. Conversely, IFNγ significantly reduced susceptibility to VV (63.1 ± 64.4-fold). The IL-4 + IL-13-induced viral susceptibility was reduced (44 ± 16%) by JAK1 inhibition, while the IL-22-enhanced viral susceptibility was diminished (76 ± 19%) by TYK2 inhibition. IFNγ-mediated resistance to viral infection was reversed by JAK2 inhibition (366 ± 294% increase in infection). Cytokines expressed in AD skin (IL-4, IL-13, IL-22) increase KC viral susceptibility while IFNγ is protective. JAKi that target JAK1 or TYK2 reversed cytokine-enhanced viral susceptibility, while JAK2 inhibition reduced the protective effects of IFNγ. [ABSTRACT FROM AUTHOR]

Published
2023
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25. The Effects that Antigen Density and Composition of Nanoparticles has on the Immune Response

Author

Brewer, Matthew G., Dewhurst, Stephen, Brewer, Matthew G., and Dewhurst, Stephen

Abstract

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Microbiology & Immunology, 2017., Vaccination has been the most effective method developed to minimize morbidity and mortality caused by infectious diseases. Unfortunately, there are many pathogens that presently lack a highly efficacious vaccine, most notably of which is Human Immunodeficiency Virus 1 (HIV-1) and Influenza. Contemporary methods of vaccination have included use of recombinant soluble proteins, attenuated viruses, or viral vectors expressing antigens. Unfortunately, all of these methods have been insufficient for developing highly effective vaccines for the above viruses. Recently, nanoparticles (NP) have emerged as a very immunogenic and robust platform for antigen delivery to the immune response. Nanoparticles were therefore chosen as an exceedingly modifiable and novel scaffold that could be investigated for delivering antigen and improving the immune response against the surface glycoproteins of HIV and Influenza. Through the course of these studies it was discovered that decoration of viral envelope proteins on NP was able to improve the immune response. This improvement was characterized by increased B cell stimulation, antibody titers, elevated levels of antibody secreting cells (ASCs) present in immune organs and increased numbers of T follicular helper and germinal center B cells in the lymph node after immunization. These observations were surprising because they only occurred when NP were decorated at a low antigen density, which is controversial since it is generally believed that increased antigen density results in elevated immunogenicity. Additionally, the response to a naturally occurring nanoparticle, Influenza A virus, was studied to understand how an immune response is generated against both internal and external proteins. Surprisingly, it was discovered that after a primary infection the antibody isotype profile was different for surface versus internal proteins. This was characterized by a robust IgA component against both of the surface antigens, hemagglutinin a

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